90

may occur at any site, if the infecting dose overcomes thenatural resistance. In people with acquired resistance,the factors responsible for this resistance cannot, owingto the erect posture, be brought so easily and in sufficientquantity to the upper thirds of the lungs (especially onthe right side, because of the obtuse angle and longerbranches of the right pulmonary artery) ; and because ofthe differences in gaseous tension bacilli grow most

rapidly in the apical regions, and thus most lesionsoccur at the apex. That the circulatory factor does notaffect only the gaseous tension is also suggested by thecollection of siliceous dust, and the resultant scars, atthe apices,7 where the particles in the macrophagesstagnate, though elsewhere they are removed by thebronchi and lymphatic channels. This difference cannotbe due to differences in gaseous tension.

It seems unreasonable at present to regard one factoras solely responsible for the localisation of tuberculouslesions in the upper third of the lungs. While Scott’sexperiments show the undoubted importance of differ-ences in gas tensions in influencing the growth of tuberclebacilli, the factors involved in the host’s resistance cannotbe ignored. Scott’s experiments give no support toSmith’s " stream-flow " hypothesis.’ 11

7. Davson, J., Susman, W. J. Path. Bact. 1937, 45. 597. Davson,J. Ibid, 1939, 49, 483.

8. Smith. D. T.. Abernethy, R. S., Smith, G. B. jun., Bondurant,S. Amer. Rev. Tuberc. 1954, 70, 547.

9. Schoenbach, E. B., Phair, J. J. Amer. J. Hyg. 1948, 47, 177.10. Love, B. D. jun., Finland, M. Amer. J. med. Sci. 1954, 228, 534.11. Banks, H. S. Lancet, 1941. i, 104. M.R.C. War Memorandum

No. 10. H.M. Stationery Office, 1943.

SUSCEPTIBILITY OF MENINGOCOCCI

THE change in the susceptibility of many strains of pathogenic staphylococci to penicillin (and in some cases ’

to the antibiotics administered by mouth), and the

emergence in the late war of sulphonamide-resistant ’

haemolytic streptococci and gonococci, point to the needfor periodic re-evaluation of the chemotherapy of infections. Surprisingly, in meningococcal meningitissulphadiazine has remained the drug of choice for

upwards of fifteen years. During the war-time epidemicsin the U.S.A. the sensitivity of meningococci to sulpha-diazine decreased very little, 9 and this decrease has neverbeen shown to have materially affected the clinicalresponse to the drug.Love and Finland 10 have tested the in-vitro sensitivity

of 50 recently isolated strains of meningococci to elevenantibiotics and to sulphadiazine. Weight for weight,penicillin was by far the most active agent and erythro-mycin ranked next, while polymyxin B and bacitracinwere the least active. Sulphadiazine, chloramphenicol,aureomycin, oxytetracycline, tetracycline, streptomycin,neomycin, and carbomycin had intermediate activity.The strains varied within a narrow range in their sensitivityto each of the antibiotics, but their susceptibility to

sulpha diazine varied over a wide range. Of the 50

strains, 6 were moderately resistant to sulphadiazineaccording to the in-vitro test used, but the remainderwere completely inhibited by 50 µg. per ml. (5 mg. per100 ml.) or less-which is well below the highest levelof sulphonamide that can readily be maintained in theblood and cerebrospinal fluid of patients. Even the 6rather more refractory strains might have been inhibitedby the dosage of sulphonamide used in Great Britain forsevere infections.l1 Comparison with the sensitivities ofstrains isolated and tested in or before 1945 gave noevidence of increasing resistance of meningococci to

penicillin.It would seem from these results that sulphadiazine

should still be the drug of choice in meningococcalmeningitis, but that in the exceptional case where theclinical response seems to be delayed sulphadiazinemight usefully be supplemented by chloramphenicolorally (since it penetrates well into the cerebrospinalfluid) or by penicillin intramuscularly and intrathecally.

ELECTROLYTE DEPLETION IN PYLORIC STENOSISJUST as the hope of a universal therapia magna sterili-

sans, aroused by the discovery of antibiotics, has beendimmed by the emergence of bacterial resistance and drug-sensitivity reactions, so the quest for " a few simplerules" in treating electrolyte disorders seems doomedto failure because of the complexity of the disturb.ances. Commonlv further disturbance is created bvtreatment directed at a single biochemical abnormality.The use of ammonium chloride to reduce a raised alkalireserve may be a case in point ; for such treatment wouldaggravate any concurrent depletion of base, and waterintoxication has in fact been observed in infants with

pyloric stenosis treated in this way.2 There may even befallacies in arguing from the composition of the fluid lostfrom the body to the likely electrolyte disorder ; for thehomoeostatic mechanisms for one ion may be more

efficient than for another, so that the final result willnot be a simple subtraction of the fluid lost from a11 normal " body-fluid. but will be modified by changesin renal excretion of ions, and possibly by transfers ofions between cells and extracellular fluid.

Black and Jepson,3 in balance studies on pyloricstenosis in adults, have defined the varied patterns ofelectrolyte depletion that may -be found in differentpatients ; and they suggest that the raised alkali reservecommonly found in patients with this condition may notbe simply explained in terms of alkalosis consequent onloss of chloride in the vomited material. During recoveryfive patients with pyloric stenosis retained amounts ofsodium, chloride, and potassium considerably greaterthan the amounts retained by patients who had under-gone partial gastrectomy for peptic ulcer uncomplicatedby stenosis. The retention of base (sodium + potassium)was greater than that of chloride, suggesting that theoriginal depletion had been of base even more than ofchloride. The patients varied considerably in the

proportion of sodium to potassium in the retained base,some having been dehydrated and others retaining morepotassium than sodium. In seeking to account for thedisappearance of

" alkalosis " observed on a regime whichactually provided more base than chloride, Black andJepson postulate that the alkalosis demonstrable in extracellular fluid was matched by an even greater intracellular-fluid acidosis. Evidence of this feature in association with potassium depletion has been found

experimentally both in animals 4 and in man.5 Further studies by Darrow’s group 6 demonstrate that rats given a high intake of bicarbonate will have an increased serum- bicarbonate level only when their potassium intake is ;

severely restricted ; and that the " alkalosis " theninduced can be corrected by potassium bicarbonate.

These observations tend to emphasise depletion of

potassium rather than of chloride as the cause of extra-cellular alkalosis in patients with pyloric stenosis.Potassium depletion has also been demonstrated in pyloricstenosis by the finding of low serum levels,7 by musclebiopsy,8 and by an observed increase in exchangeablepotassium during recovery.9 Black and Jepson suggestthat administration of saline, which accentuates potas-sium loss, should -be reserved for patients who are

clinically dehydrated. Potassium salts should be givenby mouth, and there is some evidence that these may beabsorbed even before the obstruction has been relievedby operation. These workers condemn ammonium

1. Bodansky, O. Amer. J. med. Sci. 1949, 218, 567.2. Doxiadis, S. A., Goldfinch, M. K., Holt, K. S. Lancet, 1953,

ii, 801.3. Black, D. A. K., Jepson, R. P. Quart. J. Med. 1954, 23, 367.4. Cooke, R. E., Segar, W. E., Cheek, D. B., Coville, F. E., Darrow,

D. C. J. clin. Invest. 1952, 31, 798.5. Black, D. A. K., Milne, M. D. Clin. Sci. 1952, 11, 397.6. Cooke, R. E., Segar, W. E., Reed, C., Etzwiler, D. D., Vita, M.,

Brusilow, S., Darrow, D. C. Amer. J. Med. 1954, 17, 180.7. Lans, H. S., Stein, I. F., Meyer, K. A. Ann. Surg. 1952, 135, 441.8. Mudge, G. H., Vislocky, K. J. clin. Invest. 1949, 28, 482.9. Moore, F. D., Edelman, I. S., Olney, J. M., James, A. H., Brooks,

L., Wilson, G. M. Metabolism, 1954, 3, 334.

91

chloride in view of the absence of any chloride deficit not.. covfi’pd

"

by an equal or greater deficit of base. In

addition to the risk of water intoxication, ammoniumchloride given in these circumstances might be expected

-) lead to further loss of base from the body, and to

aggravate the intracellular acidosis.

Beterman, E. M. M., Thomas, G. T. Brit. Heart J. 1953, 15, 113.— Williams, C., Soutter, L. Arch, intern. Med. 1954, 94, 571.

VISCERAL EPILEPSY

RECHT work on the electrical activity of the brainhas ’trellgthenec1 the clinical impression of over fiftyvears’ standing that paroxysmal visceral disturbance

may sometimes be epileptic. The syndrome is of interestfor several reasons. First it is a problem in diff’erentialdiagnosis; and if it is not recognised, needless alarm andabdominal operations may ensue. Secondly, the clinicalpicture is contributing to our knowledge of visceralrepresentation in the cortex : the association of visceral

epilepsy with a local cerebral lesion or a focus of abnormalelectrical discharge has shown that the medial aspectof the temporal lobe is involved in visceral activity andsensation. Finally such cases display the linkage betweenepilepsy and migraine ; for the paroxysmal visceraldisturbance of cyclical vomiting, which is widelyrecognised as a prelude to migraine in adult life, is

very occasionally associated also with later epilepticattacks, with or without, migraine. Dr. Wallis elsewhereill this issue describes some cases of the condition. His

deseriptive terrm " masked epilepsy

" is perhaps unfor-nmate. since it harks back to a time when both theclimical and the electro-encephalographic pictures ofvisceral epilepsy were less well defined. Nevertheless,his cases illustrate well the clinical setting and the

diagnostic pitfalls. Usually the disorder first shows itselfin childhood, and anticonvulsant drugs are valuableboth in diagnosis and in treatment.

DIAGNOSIS OF PERICARDIAL EFFUSION

Beterman and Thomas 1 have emphasised the valueof a rapidly enlarging heart shadow on successive radio-graphs in the diagnosis of pericardial effusion ; but this,ion i- present only before all the fluid has formed, andthen the diagnosis may be more difficult. Williams andSoutter have reviewed a series of 17 cases, all withcardiac tamponade, and found that in 11 of thesethe diagnosis was missed by at least one physician at thefirst examination. Symptoms were of little help, for theeommonest—dyspnoea—suggested heart-failure or pul-monary disease, and cough was not a constant feature.1’ain was present in half the cases, and only when thiswas substernal and worse on respiration did it seem

likely to suggest the underlying condition. Misconcep-riun: about the signs in cardiac tamponade were respon-sible for the diagnosis being missed or rejected. For

sample, often the apex-beat was regarded as too easilyfelt. or the heart sounds were thought to be too audible,for any significant amount of fluid to be present ; whileprominent ventricular pulsations on fluoroscopy, andlack of variation of the heart-shadow with position,wiongly influenced other examiners. A large effusionmay produce all the well-known signs, but it does notmvariably do so ; and the classical " quiet heart " may beeisconcertingly loud and obvious. These misconceptionswere usually based on faulty textbook statements, orclinical lore " handed on by teachers without verifi-non: but occasionally the physician was led astray’’ his own " common-sense," but incorrect, deductions.Two "ign& were often missed : a rising venous pressureand pulsus paradoxus. Increasing venous pressurewas Uiis-ed usually because the physician expectednowly distended neck veins in the upright position ;Williams and Soutter never found these, but they didand evidence of venous pulsation at the root of the neckevery patient but one. They regard this. as an impor-

tant sign of raised venous. pressure. The paradoxicalpulse, although traditionally associated with tamponade,can occur in healthy people, and be absent in those withan effusion. It is best detected by careful measurementof the systolic blood-pressure ; a drop of 10 mm. Hg ormore during inspiration suggests its presence, but thissign must be distinguished from the pulse alternationfound sometimes in left ventricular failure.

Although pericardial effusion causing tamponade iscommon, early diagnosis is important, because treat-ment may be life-saving and the diagnosis becomesincreasingly difficult as the condition worsens with fallingcardiac output and collapse. Hæmopericardium shouldbe borne in mind as a cause of tamponade : it has beendescribed 3 as a complication of anticoagulant therapyfor myocardial infarction, and so may become commoner.Here early diagnosis is especially important.

3. Goldstein, R., Wolff, L. J. Amer. med. Ass. 1951, 146, 616.4. Spillane, J. D. Nutritional Disorders of the Nervous System.

Edinburgh, 1947.5. Prickett, C. O. Amer. J. Physiol. 1934, 107, 459.6. Alexander, L. Amer. J. Path. 1940, 16, 61.7. Green, R. G., Carlson, W. E., Evans, C. A. J. Nutrit. 1941,

21, 243. Sealcook, R. R., Godland, R. L. J. Amer. chem. Soc.1944, 66, 507.

8. de Wardener, H. E., Lennox, B. Lancet, 1947, i, 11.9. Cruikshank, E. K. Quart. J. Med. 1950, 19, 327.10. Williams, R. D., Wilder, R. M., Smith, B. F. Arch. intern.

Med. 1940, 66, 785.11. Phillips, G. B., Victor, M., Adams, R. D., Davidson, C. S.

J. clin. Invest. 1952, 31, 859.12. Campbell, A. C. P., Biggart, J. H. J. Path. Bact. 1939, 48, 245.13. Feigin, I., Wolf, A. J. Pediat. 1954, 45, 243.

ENDOGENOUS VITAMIN-B1 DEFICIENCY

IT is generally - and justifiably - accepted thatWernicke’s encephalopathy is the result of aneurine

(thiamine) deficiency. In the great majority of cases 4there is clinical evidence of lack of vitamin Bl. Experi-mental deficiency in the rat 5 and pigeon s and thiaminase-induced deficiency in farm foxes produce typical cerebrallesions. In Japanese prisoner-of-war camps 8 9 wherethe diet was deficient in aneurine the condition appearedlike an epidemic. Artificial aneurine-free diets produceappropriate symptoms in volunteers,10 and preventrecovery of alcoholics otherwise adequately treated.l’The lesions of the disease have been well described,12and are highly distinctive. Oddly enough, the onlyaspect that is not fully agreed on is the clinical picture.But so many of the cases seen under ordinary circum-stances are complicated by other conditions producingcerebral symptoms of their own that this is not sur-

prising. The picture of alcoholic aneurine deficiency isparticularly confusing, and the status of Korsakow’s

syndrome in particular needs clarification. The simul-taneous presence of other vitamin deficiencies alsocommonly complicates the picture. But the carefulstudies of Phillips et al.ll have established that the casesin prisoners-of-war, described by de Wardener andLennox,8 represent the clearest-cut examples of purecerebral aneurine deficiency yet reported.

Against this more or less clear background Feiginand Wolf 13 claim to have found the lesions of Wernicke’sencephalopathy in children with no vitamin deficiency.These children were aged 2-4 years, and presented a fairlydistinctive clinical picture of a chronic disease with

inadequate growth, mental defect, ataxia, and eye signs.All appeared to have had adequate diets, and at leastone had been treated with large doses of aneurine. Alldied, and necropsy showed extensive lesions indistin-

guishable from those of classical Wernicke’s encephalo-pathy in type and distribution (it is surprising to findthe mammillary bodies unaffected in all three, but

they are by no means always involved). It is easy tocriticise this work. The number of proved cases of

’ cerebral aneurine deficiency that have been examined’

at necropsy is too few for the comparison of the histo-: logical changes to be wholly reliable. No biochemical

studies-not even pyruvic-acid levels-are recorded.